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载姜黄素壳聚糖微球的处方前研究及优化。

Formulation and optimization of zinc-pectinate beads for the controlled delivery of resveratrol.

机构信息

Department of Pharmacy, Faculty of Science, National University of Singapore, Block S4, 18 Science Drive 4, Singapore, 117543, Republic of Singapore.

出版信息

AAPS PharmSciTech. 2010 Jun;11(2):729-42. doi: 10.1208/s12249-010-9435-7. Epub 2010 May 4.

Abstract

Preventive and therapeutic efficacies of resveratrol on several lower gastrointestinal (GI) diseases (e.g., colorectal cancer, colitis) are well documented. To overcome the problems due to its rapid absorption and metabolism at the upper GI tract, a delayed release formulation of resveratrol was designed to treat these lower GI diseases. The current study aimed to develop a delayed release formulation of resveratrol as multiparticulate pectinate beads by varying different formulation parameters. Zinc-pectinate (Zn-pectinate) beads exhibited better delayed drug release pattern than calcium-pectinate (Ca-pectinate) beads. The effects of the formulation parameters were investigated on shape, size, Zn content, moisture content, drug encapsulation efficiency, swelling-erosion, and resveratrol retention pattern of the formulated beads. Upon optimization of the formulation parameters in relative to the drug release profiles, the optimized beads were further subjected to morphological, chemical interaction, enzymatic degradation, and stability studies. Almost all prepared beads were spherical with approximately 1 mm diameter and efficiently encapsulated resveratrol. The formulation parameters revealed great influence on resveratrol retention and swelling-erosion behavior. In most of the cases, the drug release data more appropriately fitted with zero-order equation. This study demonstrates that the optimized Zn-pectinate beads can encapsulate very high amount of resveratrol and can be used as delayed release formulation of resveratrol.

摘要

白藜芦醇对几种下胃肠道(GI)疾病(例如结直肠癌、结肠炎)的预防和治疗功效已有充分的文献记载。为了克服在上胃肠道快速吸收和代谢带来的问题,设计了白藜芦醇的延迟释放制剂来治疗这些下胃肠道疾病。本研究旨在通过改变不同的制剂参数,将白藜芦醇制成多颗粒果胶状珠粒的延迟释放制剂。锌-果胶(Zn-pectinate)珠粒比钙-果胶(Ca-pectinate)珠粒表现出更好的延迟药物释放模式。研究了制剂参数对形状、大小、锌含量、水分含量、药物包封效率、溶胀-侵蚀以及配方珠粒中白藜芦醇保留模式的影响。在优化制剂参数与药物释放曲线相对应后,对优化后的珠粒进行了形态学、化学相互作用、酶降解和稳定性研究。几乎所有制备的珠粒都是球形的,直径约为 1 毫米,并且能够有效地包封白藜芦醇。制剂参数对白藜芦醇保留和溶胀-侵蚀行为有很大的影响。在大多数情况下,药物释放数据更适合零级方程。本研究表明,优化的 Zn-pectinate 珠粒可以包封非常高含量的白藜芦醇,并可用作白藜芦醇的延迟释放制剂。

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